Biological systems usually expose a number of particular carbohydrates on those of their surfaces which are in contact with biological fluids, cells and tissues. Biocompatibility, bioadhesion, cell accumulation, molecular recognition, cell attachment, water retention, lubrication or defense against microbial attack are among the important functions which are thus controlled by the pattern of surface carbohydrates.
Synthetic bulk materials used for the manufacture of ophthalmic moldings in general lack the sufficient biocompatibility and affinity to maintain growth and permanent anchoring of healthy epithelial cells on their surface. A variety of different types of surface modifications has been proposed in the prior art to overcome this problem. However, the known surface coatings often do not provide the desired coating characteristics, for example cell growth ability or the ability to hold a continuous layer of an aqueous solution, e.g. human body fluids such as tears or mucus layers, for a prolonged period of time.
Surprisingly, it now has been found that the drawbacks of known bulk materials used for the manufacture of ophthalmic moldings may be overcome by covalently linking to the material surface specific carbohydrates which mimic a biological surface appropriate for cell attachment and, especially in case of contact lenses, provide high wettability, lubricity, water retention, on-eye comfort as well as longterm deposit resistance, microbial resistance and favorable lens movement on the eye.
The present invention therefore in one aspect relates to an ophthalmic molding comprising an organic bulk material having covalently bonded to its surface an acceptor saccharide to which is enzymatically attached one or more further carbohydrates selected from the group consisting of galactose, mannose, fucose, galactosamine, N-acetyl galactosamine, N-acetyl glucosamine, ialic acid and an oligosaccharide comprising one or more of the afore-mentioned arbohydrates.
Examples of suitable organic bulk materials are natural or synthetic organic polymers, for example polyaddition and polycondensation polymers (polyurethanes, epoxy resins, polyethers, polyesters, polyamides and polyimides); vinyl polymers (polyacrylates, polymethacrylates, polystyrene, polyethylene and halogenated derivatives thereof, polyvinyl acetate and polyacrylonitrile); elastomers (silicones, polybutadiene and polyisoprene); or modified or unmodified biopolymers (collagen, cellulose, chitosan and the like).
A preferred group of organic bulk materials are those being conventionally used for the manufacture of ophthalmic devices which are not hydrophilic per se. Such materials are known to the skilled artisan and may comprise for example polysiloxanes, perfluoroalkylpolyethers, fluorinated poly(meth)acrylates or equivalent fluorinated polymers derived e.g. from other polymerizable carboxylic acids, polyalkyl(meth)acrylates or equivalent alkylester polymers derived from other polymerizable carboxylic acids, or fluorinated polyolefines, such as fluorinated ethylene propylene, or tetrafluoroethylene, preferably in combination with specific dioxols, such as perfluoro-2,2-dimethyl-1,3-dioxol. Examples of suitable bulk materials are e.g. Lotrafilcon A, Neofocon, Pasifocon, Telefocon, Silafocon, Fluorsilfocon, Paflufocon, Silafocon, Elastofilcon, Fluorofocon or Teflon AF materials, such as Teflon AF 1600 or Teflon AF 2400 which are copolymers of about 63 to 73 mol % of perfluoro-2,2-dimethyl-1,3-dioxol and about 37 to 27 mol % of tetrafluoroethylene, or of about 80 to 90 mol % of perfluoro-2,2-dimethyl-1,3-dioxol and about 20 to 10 mol % of tetrafluoroethylene.
Another preferred group of organic bulk materials are those being conventionally used for the manufacture of ophthalmic devices which are derived from one or more different ethylenically unsaturated monomers comprising a hydrophilic group, for example a carboxy, carbamoyl, sulfate, sulfonate, phosphate, amine, ammonium, acetate or hydroxy group. The hydrophilic groups are inherently present in the bulk material and therefore also at the surface of a ophthalmic device manufactured therefrom. Such materials are known to the skilled artisan and comprise for example polyhydroxyethyl acrylate, polyhydroxyethyl methacrylate (HEMA), polyvinyl pyrrolidone (PVP), polyacrylic acid, polymethacrylic acid, polyacrylamide, polydimethylacrylamide (DMA), polyvinyl alcohol or copolymers for example from two or more monomers from the group hydroxyethyl acrylate, hydroxyethyl methacrylate, N-vinyl pyrrolidone, acrylic acid, methacrylic acid, acrylamide, dimethyl acrylamide, vinyl alcohol and the like. Typical examples are e.g. Polymacon, Tefilcon, Methafilcon, Deltafilcon, Bufilcon, Phemfilcon, Ocufilcon, Focofilcon, Etafilcon, Hefilcon, Vifilcon, Tetrafilcon, Perfilcon, Droxifilcon, Dimefilcon, Isofilcon, Mafilcon, Nelfilcon or Atlafilcon.
Still another group of preferred organic bulk materials are amphiphilic segmented copolymers comprising at least one hydrophobic segment, for example a polydimethylsiloxane or perfluoroalkylpolyether segment, and at least one hydrophilic segment, for example a polyoxyalkylene, poly(vinylpyrrolidone), polyhydroxyalkylacrylate or -methacrylate, polyacyl alkylene imine, polyacryl amide, polyvinyl alcohol, polyvinyl ether or polyol segment, which are linked through a direct bond or a bridge member. Examples are silicone hydrogels, for example those disclosed in PCT applications WO 96/31792 and WO 97/49740 which are herewith incorporated by reference.
Suitable acceptor saccharides comprise mono- or oligosaccharides or suitable derivatives thereof. Throughout this application the term oligosaccharide is to be understood as meaning a carbohydrate having, for example, from 2 to 20 and preferably from 2 to 10 saccharide units. The oligosaccharide may be a linear or a branched oligosaccharide. A suitable derivative of a mono- or oligosaccharide is, for example, a respective carbohydrate which is substituted by carboxy, sulfo, sulfato, thiol, amino or Nxe2x80x94C1-C4-alkanoylamino such as acetylamino, or a suitable salt thereof, or is a carbohydrate comprising a desoxyhexose.
The acceptor saccharide is preferably a mono-, di- or tri- or tetrasaccharide which in case of an oligosaccharide may be linear or branched. In one embodiment of the invention the acceptor saccharide is a mono- or disaccharide and in particular a disaccharide. Examples of preferred acceptor saccharides are thus mannose, lactose, lactobionic acid, N-acetyl lactosamine, galactose, N-acetyl galactosamine and N-acetyl glucosamine and in particular lactose, lactobionic acid, N-acetyl lactosamine or N-acetylgalactosamine. In a further embodiment of the invention the acceptor saccharide is a tetrasaccharide, in particular a branched tetrasaccharide.
The carbohydrate to be enzymatically attached to the acceptor saccharide may be one of the afore-mentioned monosaccharides or an oligosaccharide comprising at least one of said monosaccharides, for example an oligomannoside. It is preferred to enzymatically attach an afore-mentioned monosaccharide which may have any possible stereochemical configuration and preferably has the stereochemical configuration of its natural occurrence. The attachment of galactosamine or sialic acid includes suitable salts thereof. Preferably sialic acid is enzymatically attached to the acceptor saccharide. A further preferred embodiment of the invention comprises the enzymatical attachment of two or more of the afore-mentioned monosaccharides to the acceptor carbohydrate.
The covalent bonding of the acceptor saccharide to the bulk material surface may occur according to any convenient method that is known in the prior art.
According to one embodiment of the invention the ophthalmic moldings may comprise
(a) a bulk material carrying reactive groups on its surface and
(b) a surface coating obtainable by reacting the reactive groups of the bulk material surface with a functional group of the acceptor saccharide and before or after said covalent bonding of the acceptor saccharide to the bulk material enzymatically attaching the further carbohydrate(s) to the acceptor saccharide.
According to this embodiment the reactive groups on the surface of the bulk material may be reacted directly with a functional group of the acceptor saccharide which is co-reactive with the reactive groups of the bulk material, or, preferably, the acceptor saccharide is linked to the bulk material carrying reactive groups via a divalent organic spacer.
According to another embodiment of the invention, the ophthalmic moldings may comprise
(a) a bulk material having covalently bonded to its surface initiator moieties for radical polymerization; and
(b) a surface coating obtainable by grafts polymerizing one or more different acceptor saccharides comprising an ethylenically unsaturated double bond onto the bulk material surface provided with the initiator radicals and before or after said grafts polymerization enzymatically attaching the further carbohydrate(s) to the acceptor saccharide.
Suitable functional groups may be inherently (a priori) present at the surface of the bulk material. If substrates contain too few or no reactive groups, the bulk material surface can be modified by methods known per se, for example plasma chemical methods (see, for example, WO 94/06485 or WO 98/28026), or conventional functionalization with groups such as xe2x80x94OH, xe2x80x94NH2 or xe2x80x94CO2H produced. Suitable functional groups may be selected from a wide variety of groups well known to the skilled artisan. Typical examples are e.g. hydroxy groups, amino groups, carboxy groups, carbonyl groups, aldehyde groups, sulfonic acid groups, sulfonyl chloride groups, isocyanato groups, carboxy anhydride groups, lactone groups, azlactone groups, epoxy groups and groups being replaceable by amino or hydroxy groups, such as halo groups, or mixtures thereof. Preferred reactive groups on the bulk material surface are amino, hydroxy, isocyanato, isothiocyanato, glycidyl, anhydride, lactone and azlactone, in particular amino, isocyanato, glycidyl and azlactone.
One group of preferred bulk materials carrying reactive groups are bulk materials having hydroxy or in particular amino groups on their surface. Another group of preferred bulk materials carrying reactive groups concerns bulk materials which are coated with a primary polymeric coating carrying reactive groups predominantly on its surface. These primary polymeric coatings on the bulk material surface may be obtained, for example, by polymerizing an ethylenically unsaturated compound carrying a reactive group on the bulk material surface. Suitable ethylenically unsaturated compounds for this purpose are, for example, ethylenically unsaturated compounds carrying a carboxy, glycidyl, isocyanato, isothiocyanato, carboxy anhydride, lactone or azlactone group. Examples of specific unsaturated compounds carrying a reactive group are 2-isocyanatoethyl methacrylate, glycidyl methacrylate, acrylic acid anhydride, methacrylic acid anhydride or 2-vinyl-4,4-dimethyl-azlactone. Particulars concerning the preparation of a primary polymeric coating carrying reactive groups on a bulk material surface and its properties may be taken from WO 98/28026 which is herewith incorporated by reference. In case that the acceptor saccharide is linked to the bulk material surface directly or via a spacer, this may be performed, for example, by reacting the reactive groups of an organic bulk material surface as mentioned above with a compound of formula
X1xe2x80x94(R1xe2x80x94X2)uxe2x80x94(saccharide)xe2x80x83xe2x80x83(1),
wherein R1 is a divalent organic radical having from 2 to 30 C-atoms which may be further substituted,
(saccharide) is the radical of an above-mentioned acceptor saccharide or a derivative thereof,
X1 is a functional group that is co-reactive to the reactive groups on the organic bulk material surface,
X2 is a functional group linking R1 to the acceptor saccharide radical (saccharide), and
u is the number 0 or 1.
(saccharide) denotes the radical of an acceptor saccharide or a derivative thereof as mentioned above. In some cases it may be appropriate to protect a part of the hydroxy groups of the acceptor saccharide, for example, by acetylation or benzoylation, before attaching it to the bulk material surface and removing the protective groups afterwards. Suitable methods of adding and removing protective groups to/from a carbohydrate are known to the art-skilled worker in the field of carbohydrate chemistry.
Examples of a suitable radicals R1 are linear or branched C2-C30-alkylene which is unsubstituted or substituted, for example, by hydroxy, and is uninterrupted or interrupted, for example, by xe2x80x94Oxe2x80x94, xe2x80x94NRxe2x80x94 or xe2x80x94C(O)NHxe2x80x94 wherein R is hydrogen or C1-C4-alkyl; C1-C12-alkylene-C6-C10-arylen or C1-C12-alkylene-C6-C10-arylen-C1-C12-alkylene, for example C1-C12-alkylene-phenylene or C1-C12-alkylene-phenylene-C1-C12-alkylene; C1-C12-alkylene-C5-C10-cycloalkylene, for example C1-C12-alkylene-cyclohexylene or isophoronyl; C1-C12-alkylene-C5-C10-cycloalkylene-C1-C12-alkylene, for example C1-C12-alkylene-cyclohexylene-C1-C12-alkylene; or C1-C12-alkylene-heterocyclene or C1-C12-alkylene-heterocyclene-C1-C12-alkylene, wherein the heterocyclyl ring is each, for example, five- or six-membered, contains at least one N-, O- or S-atom and in addition may comprise one or more carbonyl groups, for example C1-C12-alkylene-succinimidylene or N,N-di-C1-C12-alkylene-piperazinylene.
R1 is advantageously linear or branched C2-C24-alkylene or C1-C12-alkylene-C5-C10-cycloalkylene, preferably linear or branched C4-C18-alkylene and most preferably linear C6-C10-alkylene, which in each case may be interrupted by xe2x80x94Oxe2x80x94, xe2x80x94NRxe2x80x94 or xe2x80x94C(O)NHxe2x80x94. The divalent organic spacer is most preferably a linear C2-C10 alkylene radical which is uninterrupted Hxe2x80x94or interrupted by xe2x80x94Oxe2x80x94.
X2 is, for example a group xe2x80x94C(O)Oxe2x80x94, xe2x80x94OC(O)xe2x80x94, xe2x80x94C(O)NRxe2x80x94, xe2x80x94NRC(O)xe2x80x94, xe2x80x94OC(O)NHxe2x80x94, xe2x80x94NHC(O)Oxe2x80x94, xe2x80x94NHC(S)NHxe2x80x94 or xe2x80x94NHC(O)NHxe2x80x94, and is preferably a radical xe2x80x94NHC(O)xe2x80x94, xe2x80x94NHC(O)Oxe2x80x94 or xe2x80x94C(O)Oxe2x80x94, wherein R is hydrogen or C1-C4-alkyl, and the left bond is each directed to R1 and the right bond is directed to the acceptor saccharide.
X1 is, for example, hydroxy, amino, isocyanato, isothiocyanato, carboxy or a carboxy derivative, for example a carboxy anhydride, ester, halogenid or lactone, and is preferably hydroxy, amino or isocyanato.
The variable u is an integer of 0 or preferably of 1. R is preferably hydrogen.
The compounds of formula (1) are known or may be prepared according to methods known in the art. Likewise, the reactions of a compound of formula (1) with the organic bulk material surface comprising reactive groups are well-known in the art and may be carried out as described in textbooks of organic chemistry.
According to a further embodiment of the invention the bulk material comprises covalently bonded to its surface initiator radicals for radical polymerization and a derivative of the acceptor saccharide comprising an ethylenically unsaturated double bond is grafts polymerized onto the bulk material surface provided with the initiator radicals.
Polymerization initiators bonded on the surface of the bulk material are typically those that are initiating a radical polymerization of ethylenically unsaturated compounds. The radical polymerization may be induced thermally, or preferably by irradiation.
Suitable thermal polymerization initiators are known to the skilled artisan and comprise for example peroxides, hydroperoxides, azo-bis(alkyl- or cycloalkylnitriles), persulfates, percarbonates or mixtures thereof. Examples are benzoylperoxide, tert.-butyl peroxide, di-tert.-butyl-diperoxyphthalate, tert.-butyl hydroperoxide, azo-bis(isobutyronitrile), 1,1xe2x80x2-azo-bis (1-cyclohexanecarbonitrile), 2,2xe2x80x2-azo-bis(2,4-dimethylvaleronitrile) and the like. The thermal initiators may be linked to the surface of the bulk material by methods known per se, for example as disclosed in EP-A-0378511.
Initiators for the radiation-induced polymerization are particularly functional photoinitiators having a photoinitiator part and in addition a functional group that is coreactive with functional groups of the substrate, particularly with xe2x80x94OH, xe2x80x94SH, xe2x80x94NH2, epoxy, carboxanhydride, alkylamino,xe2x80x94COOH or isocyanato groups. The photoinitiator part may belong to different types, for example to the thioxanthone type and preferably to the benzoin type. Suitable functional groups that are coreactive with the surface of the bulk material are for example a carboxy, hydroxy, epoxy or isocyanato group.
Preferred polymerization initiators for use in the present invention are the photoinitiators of formulae (I) and (Ia) as disclosed in U.S. Pat. No. 5,527,925, those of the formula (I) as disclosed in PCT application WO 96/20919, or those of formulae II and III including formulae IIa-IIy and IIg as disclosed in EP-A-0281941, particularly formulae IIb, IIi, IIm, IIn, IIp, IIr, IIs, IIx and IIIg therein. The respective portion of said three documents including the definitions and preferences given for the variables in said formulae are herewith included by reference.
The polymerization initiator moieties are preferably derived from a functional photoinitiator of the formula 
wherein Z is bivalent xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94 or xe2x80x94NR22-; Z1 is xe2x80x94Oxe2x80x94, xe2x80x94Oxe2x80x94(O)Cxe2x80x94, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or xe2x80x94Oxe2x80x94C(O)xe2x80x94Oxe2x80x94; R13 is H, C1-C12-alkyl, C1-C12-alkoxy or N-C1-C12-alkylamino; R14 and R15 are each independently of the other H, linear or branched C1-C8-alkyl, C1-C8-hydroxyalkyl or C6-C10-aryl, or the groups R14xe2x80x94(O)b1xe2x80x94 and R14xe2x80x94(O)b2xe2x80x94 together are xe2x80x94(CH2)cxe2x80x94 wherein c is an integer from 3 to 5, or the groups R14xe2x80x94(O)b1xe2x80x94, R14xe2x80x94(O)b2xe2x80x94 and R15xe2x80x94(O1)b3xe2x80x94 together are a radical of the formula 
R12 is a direct bond or linear or branched C1-C8-alkylene that is unsubstituted or substituted by xe2x80x94OH and/or is uninterrupted or interrupted by one or more groups xe2x80x94Oxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94 or xe2x80x94Oxe2x80x94C(O)xe2x80x94Oxe2x80x94; R11xe2x80x2 is branched C3-C18-alkylene, unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C6-C10-arylene, or unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C7-C18-aralkylene, unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C3-C8-cycloalkylene, unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C3-C8-cycloalkylene-CyH2yxe2x80x94 or unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted xe2x80x94CyH2yxe2x80x94(C3-C8-cycloalkylene)xe2x80x94CyH2yxe2x80x94 wherein y is an integer from 1 to 6; R16 independently has the same definitions as R11xe2x80x2 or is linear C3-C18-alkylene; R22 is linear or branched C1-C6-alkyl; T is bivalent xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Sxe2x80x94, C1-C8-alkylene or 
Z2 is a direct bond or xe2x80x94Oxe2x80x94(CH2)dxe2x80x94 wherein d is an integer from 1 to 6 and the terminal CH2 group of which is linked to the adjacent T in formula (2c); R17 is H, C1-C12-alkyl, C1-C12-alkoxy, Nxe2x80x94C1-C12-alkylamino or xe2x80x94NR25R26 wherein R25 is C1-C8-alkyl and R26 is H or C1-C8-alkyl; R18 is linear or branched C1-C8-alkyl, C2-C8-alkenyl or C6-C10-aryl-C1-C8-alkyl; R19 independently of R18 has the same definitions as R18 or is C6-C10-aryl, or R18 and R19 together are xe2x80x94(CH2)exe2x80x94 wherein e is an integer from 2 to 6; R20 and R2, are each independently of the other linear or branched C1-C8-alkyl that may be substituted by C1-C4-alkoxy, or C6-C10-aryl-C1-C8-alkyl or C2-C8-alkenyl; or R20 and R21 together are xe2x80x94(CH2)f1xe2x80x94Z3xe2x80x94(CH2)f2xe2x80x94 wherein Z3 is xe2x80x94Sxe2x80x94 or xe2x80x94NR26xe2x80x94, and R26 is H or C1-C8-alkyl and f1 and f2 are each independently of the other an integer from 2 to 4; R23 and R24 are each independently of the other H, C1-C8-alkyl, C3-C8-cycloalkyl, benzyl or phenyl; and a, a1, b1, b2 and b3 are each independently of the other 0 or 1; subject to the provisos that b1 and b2 are each 0 when R15 is H; that the total of (b1+b2+b3) is not exceeding 2; and that a is 0 when R12 is a direct bond.
A preferred sub-group of compounds of formula (2a) or (2b) comprises those wherein, b1 and b2 are each 0; Z and Z1 are each bivalent xe2x80x94Oxe2x80x94; b3 is 0 or 1; R14 is C1-C4-alkyl or phenyl, or both groups R14 together are tetramethylene or pentamethylene; R15 is C1-C4-alkyl or H, R13 is hydrogen; a and a1 are each independently 0 or 1; R12 is linear or branched C2-C4-alkylene, or is a direct bond, in which case a is 0; R11xe2x80x2 is branched C1-C10-alkylene, phenylene or phenylene substituted by from 1 to 3 methyl groups, benzylene or benzylene substituted by from 1 to 3 methyl groups, cyclohexylene or cyclohexylene substituted by from 1 to 3 methyl groups, cyclohexyl-CyH2yxe2x80x94 or xe2x80x94CyH2y-cyclohexyl-CyH2yxe2x80x94 or cyclohexyl-CyH2yxe2x80x94 or xe2x80x94CyH2y-cyclohexyl-CyH2yxe2x80x94 substituted by from 1 to 3 methyl groups; y is 1 or 2; and R16 has the same definitions as R11xe2x80x2 or is linear C3-C10alkylene.
An especially preferred sub-group of compounds of formula (2a) or (2b) comprises those wherein, b1 and b2 are each 0, Z and Z1 are each bivalent xe2x80x94Oxe2x80x94, b3 is 0 or 1; R14 is methyl or phenyl, or both groups R14 together are pentamethylene; R15 is methyl or H; R13 is hydrogen; a is 1 and R12 is ethylene, or a is 0 and R12 is a direct bond; a1 is 0 or 1; R11xe2x80x2 is branched C6-C10-alkylene, phenylene or phenylene substituted by from 1 to 3 methyl groups, benzylene or benzylene substituted by from 1 to 3 methyl groups, cyclohexylene or cyclohexylene substituted by from 1 to 3 methyl groups, cyclohexyl-CH2xe2x80x94 or cyclohexyl-CH2xe2x80x94 substituted by from 1 to 3 methyl groups; R16 has the same definitions as R11xe2x80x2 or is linear C5-C10alkylene.
A preferred sub-group of compounds of formula (2c) comprises those wherein T is bivalent xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Sxe2x80x94 or xe2x80x94(CH2)yxe2x80x94 wherein y is an integer from 1 to 6; Z2 is a direct bond or xe2x80x94Oxe2x80x94(CH2)yxe2x80x94 wherein y is an integer from 1 to 6 and the terminal CH2 group of which is linked to the adjacent T in formula (2c); R17 is H, C1-C12-alkyl or C1-C12-alkoxy; R18 is linear C1-C8-alkenyl or C6-C10-aryl-C1-C8-alkyl; R19 independently of R18 has the same definitions as R18 or is C6-C10-aryl, or R18 and R19 together are xe2x80x94(CH2)exe2x80x94 wherein e is an integer from 2 to 6; R20 and R21 are each independently of the other linear or branched C1-C8-alkyl that may be substituted by C1-C4-alkoxy, or C6-C10-aryl-C1-C8-alkyl or C2-C8-alkenyl; or R20 and R21 (CH2)f2xe2x80x94 wherein Z3 is a direct bond, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94 or xe2x80x94NR26xe2x80x94, and R26 is H or C1-C8-alkyl and f1 and F2 are each independently of the other an integer from 2 to 4; and R16 is branched C6-C10-alkylene, phenylene or phenylene substituted by from 1 to 3 methyl groups, benzylene or benzylene substituted by from 1 to 3 methyl groups, cyclohexylene or cyclohexylene substituted by from 1 to 3 methyl groups, cyclohexylene-CH2xe2x80x94 or cyclohexylene-CH2-substituted by from 1 to 3 methyl groups.
An especially preferred sub-group of compounds of formula (2c) comprises those wherein T is bivalent xe2x80x94Oxe2x80x94; Z2 is xe2x80x94Oxe2x80x94(CH2)yxe2x80x94 wherein y is an integer from 1 to 4 and the terminal CH2 group of which is linked to the adjacent T in formula (2c); R17 is H; R18 is methyl, alkyl, tolylmethyl or benzyl, R19 is methyl, ethyl, benzyl or phenyl, or R18 and R19 together are pentamethylene, R20 and R2, are each independently of the other C1-C4-alkyl or R20 and R21 together are xe2x80x94CH2CH2OCH2CH2xe2x80x94, and R16 is branched C6-C10-alkylene, phenylene or phenylene substituted by from 1 to 3 methyl groups, benzylene or benzylene substituted by from 1 to 3 methyl groups, cyclohexylene or cyclohexylene substituted by from 1 to 3 methyl groups, cyclohexylene-CH2xe2x80x94 or cyclohexylene-CH2-substituted by from 1 to 3 methyl groups.
Some examples of especially preferred functional photoinitiators are the compounds of formulae 
In a preferred embodiment of the invention, the covalent bonding between the organic bulk material and the photoinitiator occurs via reaction of a hydroxy, amino, alkylamino, thiol or carboxy group, particularly of a hydroxy or amino group, of the substrate surface with an isocyanato group of the photoinitiator, for example using a photoinitiator of the above formula (2b), (2c), (3a), (3b) or (3c). Suitable methods for this are known, for example, from the above-mentioned documents. The reaction may be carried out, for example, at elevated temperature, for example from 0xc2x0 to 100xc2x0 C. and preferably at room temperature, and optionally in the presence of a catalyst. After the reaction, excess compounds can be removed, for example, with solvents.
According to a preferred embodiment of the invention the organic bulk material is an organic polymer containing H-active groups, in particular xe2x80x94OH, xe2x80x94NH2 and/or xe2x80x94NHxe2x80x94, on the surface that are coreactive with isocyanato groups, some or all of whose H atoms have been substituted by radicals of the formulae 
wherein for the variables R11xe2x80x2-R21, T, Z, Z1, Z2, a, b1, b2 and b3 the above-given meanings and preferences apply.
In another preferred embodiment of the invention, the covalent bonding between the organic bulk material and the photoinitiator occurs via reaction of a epoxy, carboxanhydride, lactone, azlactone or preferably isocyanato group of the substrate surface with a hydroxy, amino, alkylamino, thiol or carboxy group, particularly with a carboxy, hydroxy or amino group, of the photoinitiator, for example using a photoinitiator of the above formula (2a). This may be carried out, for example, by first reacting an above-mentioned bulk material containing H-active groups on the surface, in particular xe2x80x94OH, xe2x80x94NH2 and/or xe2x80x94NH, selectively with one isocyanato group of a m diisocyanate of formula OCNxe2x80x94R11xe2x80x2xe2x80x94NCO, wherein R11xe2x80x2 has the above-given meanings, and then reacting the modified bulk material with a photoinitiator of the above-mentioned formula (2a).
Suitable derivatives of an acceptor saccharide comprising an ethylenically unsaturated double bond are, for example, those of formula 
wherein A is a radical of formula
xe2x80x94C(O)xe2x80x94(A1)nxe2x80x94Xxe2x80x94xe2x80x83xe2x80x83(6a) or
xe2x80x94(A2)mxe2x80x94NHxe2x80x94C(O)xe2x80x94Xxe2x80x94xe2x80x83xe2x80x83(6b); or
xe2x80x94C(O)xe2x80x94NHxe2x80x94C(O)xe2x80x94Xxe2x80x94xe2x80x83xe2x80x83(6c);
R2 is hydrogen, C1-C6-alkyl or a radical xe2x80x94COORxe2x80x2;
R3, R1 and R2xe2x80x2are each independently of the other hydrogen or C1-C6-alkyl;
A1 is xe2x80x94Oxe2x80x94C2-C12-alkylene which is unsubstituted or substituted by hydroxy, or is xe2x80x94Oxe2x80x94C2-C12-alkylenexe2x80x94NHxe2x80x94C(O)xe2x80x94 or xe2x80x94Oxe2x80x94C2-C12-alkylenexe2x80x94Oxe2x80x94C(O)xe2x80x94NHxe2x80x94R11xe2x80x94NHxe2x80x94C(O)xe2x80x94, wherein R11 is linear or branched C1-C18-alkylene or unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C6-C10-arylene, C7-C18-aralkylene, C6-C10-arylene-C1-C2-alkylene-C6-C10-arylene, C3-C8-cycloalkylene, C3-C8-cycloalkylene-C1-C6-alkylene, C3-C8-cycloalkylene-C1-C2-alkylene-C3-C8-cycloalkylene or C1-C6-alkylene-C3-C8-cycloalkylene-C1-C6-alkylene;
A2 is C1-C8-alkylene; phenylene or benzylene;
m and n are each independently of the other the number 0 or 1;
X is a bivalent group xe2x80x94Oxe2x80x94 or xe2x80x94NRxe2x80x3, wherein Rxe2x80x3 is hydrogen or C1-C6-alkyl; and
R1, X2, u and (saccharide) are each as defined above.
The following preferences apply to the variables contained in the definition of the macromonomer of formula (5):
R1 is preferably hydrogen or C1-C4-alkyl, more preferably hydrogen or C1-C2-alkyl and particularly preferably hydrogen.
R2is preferably hydrogen, methyl or carboxyl, and particularly preferably hydrogen.
R2xe2x80x2 is preferably hydrogen or methyl and particularly preferably hydrogen.
R3 is preferably hydrogen or methyl.
X is preferably a bivalent group xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94 and in particular a bivalent group xe2x80x94Oxe2x80x94.
The radical R11 has a symmetrical or, preferably, an asymmetrical structure. A preferred group of radicals R11 comprises those, wherein R11 is linear or branched C6-C10alkylene; cyclohexylene-methylene or cyclohexylene-methylene-cyclohexylene each unsubstituted or substituted in the cyclohexyl moiety by from 1 to 3 methyl groups; or phenylene or phenylene-methylene-phenylene each unsubstituted or substituted in the phenyl moiety by methyl. The bivalent radical R11 is derived preferably from a diisocyanate and most preferably from a diisocyanate selected from the group isophorone diisocyanate (IPDI), toluylene-2,4-diisocyanate (TDI), 4,4xe2x80x2-methylenebis(cyclohexyl isocyanate), 1,6-diisocyanato-2,2,4-trimethyl-n-hexane (TMDI), methylenebis(phenyl isocyanate), methylenebis(cyclohexyl-4-isocyanate) and hexamethylene diisocyanate (HMDI).
Preferred meanings of A1 are unsubstituted or hydroxy-substituted xe2x80x94Oxe2x80x94C2-C8-alkylene or a radical xe2x80x94Oxe2x80x94C2-C6-alkylenexe2x80x94NHxe2x80x94C(O)xe2x80x94 and particularly xe2x80x94Oxe2x80x94(CH2)2-4xe2x80x94, xe2x80x94Oxe2x80x94CH2xe2x80x94CH(OH)xe2x80x94CH2xe2x80x94 or radical xe2x80x94Oxe2x80x94(CH2)2-4xe2x80x94NHxe2x80x94C(O)xe2x80x94. A particularly preferred meaning of A, is the radical xe2x80x94Oxe2x80x94(CH2)2xe2x80x94NHxe2x80x94C(O)xe2x80x94.
A2 is preferably C1-C6-alkylene, phenylene or benzylene, more preferably C1-C4-alkylene and even more preferably C1-C2-alkylene.
n is an integer of 0 or preferably 1. m is preferably an integer of 1.
Regarding the variables R1, X2, u and (saccharide), each the above-given meanings and preferences apply.
A preferred group of ethylenically unsaturated acceptor saccharides according to the invention comprises compounds of the above formula (5), wherein R3 is hydrogen or methyl, R2 is hydrogen, methyl or carboxyl, R2xe2x80x2 is hydrogen, A is a radical of the formula (6a) or (6b), R1 is linear or branched C2-C24-alkylene,uninterrupted or interrupted by xe2x80x94Oxe2x80x94, xe2x80x94NRxe2x80x94 or xe2x80x94C(O)NHxe2x80x94, X2 is a radical xe2x80x94C(O)Oxe2x80x94, xe2x80x94OC(O)xe2x80x94, xe2x80x94C(O)NRxe2x80x94, xe2x80x94NRC(O)xe2x80x94, xe2x80x94OC(O)NHxe2x80x94, xe2x80x94NHC(O)Oxe2x80x94, xe2x80x94NHC(S)NHxe2x80x94 or xe2x80x94NHC(O)NHxe2x80x94, R is each independently hydrogen or C1-C4-alkyl, u is the number 0 or 1, and (saccharide) is the radical of a mono-, di-, tri- or tetrasaccharide. An even more preferred group of ethylenically unsaturated acceptor saccharides comprises compounds of the above formula (5), wherein R3 is hydrogen or methyl, R2 and R2xe2x80x2 are each hydrogen, A is a radical of the formula (6a), u is the number 1, R1 is linear C2-C10 alkylene radical which is uninterrupted or interrupted by xe2x80x94Oxe2x80x94, X2 is a radical xe2x80x94NHC(O)xe2x80x94, xe2x80x94NHC(O)Oxe2x80x94 or xe2x80x94C(O)Oxe2x80x94, and (saccharide) is the radical of a disaccharide.
The acceptor saccharide derivatives of formula (5) may be prepared by methods known per se. For example, the compounds of formula (5) are obtainable by reacting a compound of formula 
wherein R2, R2xe2x80x2 and R3 each have the above-given meaning and A* is, for example, a group xe2x80x94C(O)xe2x80x94A**, wherein A** is halogen, particularly chlorine, an ester group an oxyalkylene radical comprising an epoxy group, for example the radical 
or is a radical xe2x80x94Oxe2x80x94)C2-C12-alkylene-Nxe2x95x90Cxe2x95x90O; or A* is a radical xe2x80x94(A2)mxe2x80x94Nxe2x95x90Cxe2x95x90O, wherein A2 and m have the above-given meaning, with a compound of formula
HXxe2x80x94(R1xe2x80x94X2)uxe2x80x94(saccharide)xe2x80x83xe2x80x83(8),
wherein R1, X1 X2, u and (saccharide) each have the above-given meaning.
The reactions of a compound of formula (7) having a carboxylic acid halide group, an epoxy group or an isocyanato group with an amino or hydroxy compound of formula (8) are well-known in the art and may be carried out as described in textbooks of organic chemistry. For example, the reaction of an isocyanato derivative of formula (7) with a compound of formula (8) may be carried out in an inert organic solvent such as an optionally halogenated hydrocarbon, for example petrolium ether, methylcyclohexane, toluene, chloroform, methylene chloride and the like, or an ether, for example diethyl ether, tetrahydrofurane, dioxane, or a more polar solvent such as DMSO, DMA, N-methylpyrrolidone or even a lower alcohol, at a temperature of from 0 to 100xc2x0 C., preferably from 0 to 50xc2x0 C. and particularly preferably at room temperature, optionally in the presence of a catalyst, for example a tertiary amine such as triethylamine or tri-n-butylamine, 1,4-diazabicyclooctane, or a tin compound such as dibutyltin dilaurate or tin dioctanoate. In addition, the reaction of an isocyanato derivative of formula (7) with a compound of formula (8) wherein xe2x80x94XH is an amino group also may be carried out in an aqueous solution in the absence of a catalyst. It is advantageous to carry out the above reactions under an inert atmosphere, for example under an nitrogen or argon atmosphere.
The derivatives of the acceptor saccharide comprising an ethylenically unsaturated double bond, for example, of formula (5) may be applied to the initiator-modified bulk material surface and polymerized there according to processes known per se. For example, the bulk material is immersed in a solution of the double bond modified acceptor saccharide, or a layer of the double bond modified acceptor saccharide is first of all deposited on the modified bulk material surface, or example, by dipping, spraying, spreading, knife coating, pouring, rolling, spin coating or vacuum vapor deposition. The polymerization of the modified acceptor saccharide on the bulk material surface then may be initiated, for example, thermally by the action of heat or preferably by irradiation, particularly by UV radiation. Suitable light sources for the irradiation are known to the artisan and comprise for example mercury lamps, high pressure mercury lamps, xenon lamps, carbon arc lamps or sunlight. The time period of irradiation may depend for example on the desired properties of the resulting composite material but is usually in the range of up to 30 minutes, preferably from 10 seconds to 10 minutes, and particularly preferably from 0.5 to 5 minutes. It is advantageous to carry out the irradiation in an atmosphere of inert gas. After the polymerization, any non-covalently bonded acceptor saccharide can be removed, for example by treatment with suitable solvents.
Whereas one feature of this embodiment of the invention comprises to polymerize one or more different derivatives of an acceptor saccharide comprising an ethylenically unsaturated double bond onto the surface of the ophthalmic molding as outlined above, another feature of this embodiment of the invention comprises to copolymerize one or more above-mentioned ethylenically unsaturated acceptor saccharides with one or more different hydrophilic macromonomers onto the surface.
Suitable macromonomers correspond, for example, to formula 
wherein R4 independently has the meaning of R2, R4xe2x80x2 independently has the meaning of R2xe2x80x2, R4* independently has the meaning of R3, A3 independently has the meaning of A or is a radical of formula
xe2x80x94(A4)txe2x80x94X3xe2x80x94C(O)xe2x80x94xe2x80x83xe2x80x83(6d); or
xe2x80x94C(O)xe2x80x94X4xe2x80x94(alk*)xe2x80x94X3xe2x80x94C(O)xe2x80x94xe2x80x83xe2x80x83(6e); or
A3 and R4, together with the adjacent double bond, are a radical of formula 
Xxe2x80x2 X3, X4 and X5 are each independently of the other a bivalent group xe2x80x94Oxe2x80x94 or xe2x80x94NR* wherein R* is hydrogen or C1-C6-alkyl;
A4 independently has the meaning of A2 above;
t is an integer of 0 or 1;
(alk*) is C2-C12-alkylene;
and (oligomer) denotes the radical of a telomer of formula 
xe2x80x83wherein (alk) is C2-C12-alkylene,
Q is a monovalent group that is suitable to act as a polymerization chain-reaction terminator,
p and q are each independently of another an integer from 0 to 100, wherein the total of (p+q) is an integer from 2 to 250,
and B and Bxe2x80x2 are each independently of the other a 1,2-ethylene radical derivable from a copolymerizable vinyl monomer by replacing the vinylic double bond by a single bond, at least one of the radicals B and Bxe2x80x2 being substituted by a hydrophilic substituent;
The following preferences apply to the variables contained in formulae (6d), (6e), (6f), (9) and (10):
For R4 independently the meanings and preferences given above for R2 apply.
For R4xe2x80x2 independently the meanings and preferences given above for R2xe2x80x2 apply.
For R4* independently the meanings and preferences given above for R3 apply.
For A4 independently the meanings and preferences given above for A2 apply.
t is preferably an integer of 1.
Xxe2x80x2 and X3 are each independently preferably a group xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94 and in particular a group xe2x80x94NHxe2x80x94.
X4 and X5 are each independently preferably a group xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94.
(alk) and (alk*) are each independently preferably C2-C8-alkylene, more preferably C2-C6-alkylene, even more preferably C2-C4-alkylene and particularly preferably 1,2-ethylene. The alkylene radicals (alk) and (alk*) may be branched or preferably linear alkylene radicals.
A3 preferably denotes a radical of formula (6a) or (6b) given above and particularly preferably a radical of formula (6a), wherein the above given meanings and preferences apply for the variables contained therein.
A preferred group of hydrophilic macromonomers comprises compounds of the above formula (9), wherein R4* is hydrogen or methyl, R4 is hydrogen, methyl or carboxyl, R4xe2x80x2 is hydrogen, and A3 is a radical of the formula (6a) or (6b). An even more preferred group of hydrophilic macromonomers comprises compounds of the above formula (9), wherein R4* is hydrogen or methyl, R4 and R4xe2x80x2 are each hydrogen, and A3 is a radical of the formula (2a). A further group of preferred hydrophilic macromonomers comprises compounds of formula (9), wherein A3 is a radical of formula (6e) above. Q is for example hydrogen.
The total of (p+q) is preferably an integer from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 10 to 50. In a preferred embodiment of the invention q is 0 and p is an integer from 2 to 250, preferably from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 10 to 50.
Suitable hydrophilic substituents of the radicals B or Bxe2x80x2 may be non-ionic, anionic, cationic or zwitterionic substituents. Accordingly, the telomer chain of formula (10) that contains monomer units B and/or Bxe2x80x2 may be a charged chain containing anionic, cationic and/or zwitterionic groups or may be an uncharged chain. In addition, the telomer chain may comprise a copolymeric mixture of uncharged and charged units. The distribution of the charges within the telomer, if present, may be random or blockwise.
In one preferred embodiment of the invention, the telomer radical of formula (10) is composed solely of non-ionic monomer units B and/or Bxe2x80x2. In another preferred embodiment of the invention, the telomer radical of formula (10) is composed solely of ionic monomer units B and/or Bxe2x80x2, for example solely of cationic monomer units or solely of anionic monomer units. Still another preferred embodiment of the invention is directed to telomer radicals of formula (10) comprising nonionic units B and ionic units Bxe2x80x2.
Suitable non-ionic substituents of B or Bxe2x80x2 include for example a radical C1-C6-alkyl which is substituted by one or more same or different substituents selected from the group consisting of xe2x80x94OH, C1-C4-alkoxy and xe2x80x94NR9R9xe2x80x2, wherein R9 and R9xe2x80x2 are each independently of another hydrogen or unsubstituted or hydroxy-substituted C1-C6-alkyl or phenyl; phenyl which is substituted by hydroxy, C1-C4-alkoxy or xe2x80x94NR9R9xe2x80x2, wherein R9 and R9xe2x80x2 are as defined above; a radical xe2x80x94COOY, wherein Y is C1-C24-alkyl which is unsubstituted or substituted, for example, by hydroxy, C1-C4-alkoxy, xe2x80x94Oxe2x80x94Si(CH3)3, xe2x80x94NR9R9xe2x80x2 wherein R9 and R9xe2x80x2 are as defined above, a radical xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94E wherein E is hydrogen or C1-C6-alkyl, or a radical xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94(CH2CH2O)1-24-E, wherein E is as defined above, or Y is C5-C8-cycloalkyl which is unsubstituted or substituted by C1-C4-alkyl or C1-C4-alkoxy, or is unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted phenyl or C7-C12-aralkyl; xe2x80x94CONY1Y2 wherein Y1 and Y2 are each independently hydrogen, C1-C12-alkyl, which is unsubstituted or substituted for example by hydroxy, C1-C4-alkoxy or a radical xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94E wherein E is as defined above, or Y1 and Y2 together with the adjacent N-atom form a five- or six-membered heterocyclic ring having no additional heteroatom or one additional oxygen or nitrogen atom; a radical xe2x80x94OY3, wherein Y3 is hydrogen; or C1-C12-alkyl which is unsubstituted or substituted by xe2x80x94NR9R9xe2x80x2; or is a radical xe2x80x94C(O)xe2x80x94C1-C4-alkyl; and wherein R9 and R9xe2x80x2 are as defined above; or a five- to seven-membered heterocyclic radical having at least one N-atom and being bound in each case via said nitrogen atom.
Suitable anionic substituents of B or Bxe2x80x2 include for example C1-C6-alkyl which is substituted by xe2x80x94SO3H, xe2x80x94OSO3H, xe2x80x94OPO3H2 and xe2x80x94COOH; phenyl which is substituted by one or more same or different substituents selected from the group consisting of xe2x80x94SO3H, xe2x80x94COOH, xe2x80x94OH and xe2x80x94CH2xe2x80x94SO3H; xe2x80x94COOH; a radical xe2x80x94COOY4, wherein Y4 is C1-C24-alkyl which is substituted for example by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, or xe2x80x94OPO3H2; a radical xe2x80x94CONY5Y6 wherein Y5 is C1-C24-alkyl which is substituted by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, or xe2x80x94OPO3H2 and Y6 independently has the meaning of Y5 or is hydrogen or C1-C12-alkyl; or xe2x80x94SO3H; or a salt thereof, for example a sodium, potassium, ammonium or the like salt thereof.
Suitable cationic substituents of B or Bxe2x80x2 include C1-C12-alkyl which is substituted by a radical xe2x80x94NR9R9xe2x80x2R9xe2x80x3+Anxe2x88x92, wherein R9, R9xe2x80x2 and R9xe2x80x3 are each independently of another hydrogen or unsubstituted or hydroxy-substituted C1-C6-alkyl or phenyl, and Anxe2x88x92 is an anion; or a radical xe2x80x94C(O)OY7, wherein Y7 is C1-C24-alkyl which is substituted by xe2x80x94NR9R9xe2x80x2, R9xe2x80x3+Anxe2x88x92 and is further unsubstituted or substituted for example by hydroxy, wherein R9, R9xe2x80x2, R9xe2x80x3 and Anxe2x88x92 are as defined above.
Suitable zwitterionic substituents of B or Bxe2x80x2 include a radical xe2x80x94R5xe2x80x94Zw, wherein R5 is a direct bond or a functional group, for example a carbonyl, carbonate, amide, ester, dicarboanhydride, dicarboimide, urea or urethane group; and Zw is an aliphatic moiety comprising one anionic and one cationic group each.
The following preferences apply to the hydrophilic substituents of B and Bxe2x80x2:
(i) Non-ionic Substituents:
Preferred alkyl substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is substituted by one or more substituents selected from the group consisting of xe2x80x94OH and xe2x80x94NR9R9xe2x80x2, wherein R9 and R9xe2x80x2 are each independently of another hydrogen or C1-C4-alkyl, preferably hydrogen, methyl or ethyl and particularly preferably hydrogen or methyl, for example xe2x80x94CH2xe2x80x94NH2, xe2x80x94CH2xe2x80x94N(CH3)2.
Preferred phenyl substituents of B or Bxe2x80x2 are phenyl which is substituted by xe2x80x94NH2 or N(C1-C2-alkyl)2, for example o-, m- or p-aminophenyl.
In case that the hydrophilic substituent of B or Bxe2x80x2 is a radical xe2x80x94COOY, Y as optionally substituted alkyl is preferably C1-C12-alkyl, more preferably C1-C6-alkyl, even more preferably C1-C4-alkyl and particularly preferably C1-C2-alkyl, each of which being unsubstituted or substituted as mentioned above. In case that the alkyl radical Y is substituted by xe2x80x94NR9R9xe2x80x2, the above-given meanings and preferences apply for R9 and R9xe2x80x2. In case that the alkyl radical Y is substituted by a radical xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94E or xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94E, the number of (CH2CH2O) units is preferably from 1 to 12 in each case and more preferably from 2 to 8. E is preferably hydrogen or C1-C2-alkyl.
Y as C5-C8-cycloalkyl is for example cyclopentyl or preferably cyclohexyl, each of which being unsubstituted or substituted for example by 1 to 3 C1-C2-alkyl groups. Y as C7-C12-aralkyl is for example benzyl.
Preferred nonionic radicals xe2x80x94COOY are those wherein Y is C1-C6-alkyl; or C2-C6-alkyl which is substituted by one or two substituents selected from the group consisting of hydroxy; C1-C2-alkoxy; xe2x80x94Oxe2x80x94Si(CH3)3; and xe2x80x94NR9R9xe2x80x2 wherein R9 and R9xe2x80x2 are each independently of another hydrogen or C1-C4-alkyl; or Y is a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH2O)1-12-E wherein E is hydrogen or C1-C2-alkyl.
More preferred non-ionic radicals xe2x80x94COOY are those wherein Y is C1-C4-alkyl; or C2-C4-alkyl which is substituted by one or two substituents selected from the group consisting of xe2x80x94OH and xe2x80x94NR9R9xe2x80x2 wherein R9 and R9xe2x80x2 are each independently of another hydrogen or C1-C2-alkyl; or a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH2O)1-12xe2x80x94E wherein E is hydrogen or C1-C2-alkyl.
Particularly preferred radicals xe2x80x94COOY comprise those wherein Y is C1-C2-alkyl, particularly methyl; or C2-C3-alkyl, which is unsubstituted or substituted by hydroxy or N,N-di-C1-C2-alkylamino.
Preferred non-ionic substituents xe2x80x94C(O)xe2x80x94NY1Y2 of B or Bxe2x80x2 are those wherein Y1 and Y2 are each independently of the other hydrogen or C1-C6-alkyl which is unsubstituted or substituted by hydroxy; or Y1 and Y2 together with the adjacent N-atom form a heterocyclic 6-membered ring having no further heteroatom or having one further N- or O-atom. Even more preferred meanings of Y1 and Y2, independently of each other, are hydrogen or C1-C4-alkyl which is unsubstituted or substituted by hydroxy; or Y1 and Y2 together with the adjacent N-atom form a Nxe2x80x94C1-C2-alkylpiperazino or morpholino ring. Particularly preferred non-ionic radicals xe2x80x94C(O)xe2x80x94NY1Y2 are those wherein Y1 and Y2 are each independently of the other hydrogen or C1-C2-alkyl; or Y1 and Y2 together with the adjacent N-atom form a morpholino ring.
Preferred non-ionic substituents xe2x80x94OY3 of B or Bxe2x80x2 are those wherein Y3 is hydrogen, C1-C4-alkyl which is unsubstituted or substituted by xe2x80x94NH2 or xe2x80x94N(C1-C2-alkyl)2, or is a group xe2x80x94C(O)C1-C2-alkyl. Y3 is particularly preferred hydrogen or acetyl.
Preferred non-ionic heterocyclic substituents of B or Bxe2x80x2 are a 5- or 6-membered heteroaromatic or heteroaliphatic radical having one N-atom and in addition no further heteroatom or an additional Nxe2x80x94 or Oxe2x80x94 heteroatom, or is a 5 to 7-membered lactame. Examples of such heterocyclic radicals are N-pyrrolidonyl, 2- or 4-pyridinyl, 2-methyl pyridin-5-yl, 2-, 3- oder 4-hydroxypyridinyl N-xcex5-caprolactamyl, N-imidazolyl, 2-methylimidazol-1-yl, N-morpholinyl or 4-N-methylpiperazin-1-yl, particularly N-morpholinyl or N-pyrrolidonyl.
A group of preferred non-ionic substituents of B or Bxe2x80x2 comprises C1-C2-alkyl, which is unsubstituted or substituted by xe2x80x94OH or xe2x80x94NR9R9xe2x80x2, wherein R9 and R9xe2x80x2 are each independently of the other hydrogen or C1-C2-alkyl; a radical xe2x80x94COOY wherein Y is C1-C4-alkyl; C2-C4-alkyl which is substituted by xe2x80x94OH, xe2x80x94NR9R9xe2x80x2 wherein R9 and R9xe2x80x2 are each independently of another hydrogen or C1-C2-alkyl; a radical xe2x80x94C(O)xe2x80x94NY1Y2, herein Y1 and Y2 are each independently of the other hydrogen or C1-C6-alkyl which is unsubstituted or substituted by hydroxy, or Y1 and Y2 together with the adjacent N-atom form a heterocyclic 6-membered ring having no further heteroatom or having one further N- or O-atom; a radical xe2x80x94OY3, wherein Y3 is hydrogen, C1-C4-alkyl which is unsubstituted or substituted by xe2x80x94NH2 or xe2x80x94N(C1-C2-alkyl)2, or is a group xe2x80x94C(O)C1-C2-alkyl; or a 5- or 6-membered heteroaromatic or heteroaliphatic radical having one N-atom and in addition no further heteroatom or an additional N-, O- or S-heteroatom, or a 5 to 7-membered lactame.
A group of more preferred non-ionic substituents of B or Bxe2x80x2 comprises a radical xe2x80x94COOY, wherein Y is C1-C2-alkyl, C2-C3-alkyl, which is substituted by hydroxy, amino or N,N-di-C1-C2-alkylamino; a radical xe2x80x94COxe2x80x94NY1Y2, wherein Y1 and Y2 are each independently of the other hydrogen or C1-C4-alkyl which is unsubstituted or substituted by hydroxy, or Y1 and Y2 together with the adjacent N-atom form a Nxe2x80x94C1-C2-alkylpiperazino or morpholino ring; or a heterocyclic radical selected from the group consisting of N-pyrrolidonyl, 2- or 4-pyridinyl, 2-methylpyridin-5-yl, 2-, 3- oder 4- hydroxypyridinyl, N-F-caprolactamyl, N-imidazolyl, 2-methylimidazol-1-yl, N-morpholinyl and 4-N-methylpiperazin-1-yl.
A particularly preferred group of non-ionic substituents of B or Bxe2x80x2 comprises the radicals xe2x80x94COOxe2x80x94C1-C2-alkyl, xe2x80x94COOxe2x80x94(CH2)2-4xe2x80x94OH, xe2x80x94CONH2, xe2x80x94CON(CH3)2, xe2x80x94CONHxe2x80x94(CH2)2xe2x80x94OH, 
(ii) Anionic Substituents:
Preferred anionic substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is substituted by one or more substituents selected from the group consisting of xe2x80x94SO3H and xe2x80x94OPO3H2, for example xe2x80x94CH2xe2x80x94SO3H; phenyl which is substituted by xe2x80x94SO3H or sulfomethyl, for example o-, m- or p-sulfophenyl or o-, m- or p-sulfomethylphenyl; xe2x80x94COOH; a radical xe2x80x94COOY4, wherein Y4 is C2-C6-alkyl which is substituted by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, xe2x80x94OPO3H2, in particular C2-C4-alkyl which is substituted by xe2x80x94SO3H or xe2x80x94OSO3H; a radical xe2x80x94CONY5Y6 wherein Y5 is C1-C6-alkyl substituted by sulfo, in particular C2-C4-alkyl substituted by sulfo, and Y6 is hydrogen, for example the radical xe2x80x94C(O)xe2x80x94NHxe2x80x94C(CH3)2xe2x80x94CH2xe2x80x94SO3H; or xe2x80x94SO3H; or a suitable salt thereof. Particular preferred anionic substituents of B or Bxe2x80x2 are xe2x80x94COOH, xe2x80x94SO3H, o-, m- or p-sulfophenyl, o-, m- or p-sulfomethylphenyl or a radical xe2x80x94CONY5Y6 wherein Y5 is C2-C4-alkyl substituted by sulfo, and Y6 is hydrogen.
(iii) Cationic Substituents:
Preferred cationic substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is in each case substituted by xe2x80x94NR9R9xe2x80x2R9xe2x80x3+Anxe2x88x92; or a radical xe2x80x94C(O)OY7 wherein Y7 is C2-C6-alkyl, in particular C2-C4-alkyl, which is in each case substituted by xe2x80x94NR9R9xe2x80x2R9xe2x80x3+Anxe2x88x92 and is further unsubstituted or substituted by hydroxy. R9, R9xe2x80x2 and R9xe2x80x3 are each independently of another preferably hydrogen or C1-C4-alkyl, more preferably methyl or ethyl and particularly preferably methyl. Examples of suitable anions Anxe2x88x92 are Halxe2x88x92, wherein Hal is halogen, for example Brxe2x88x92, Fxe2x88x92, Jxe2x88x92 or particularly Clxe2x88x92, furthermore HCO3xe2x88x92, CO32xe2x88x92, H2PO3xe2x88x92, HPO32xe2x88x92, PO33xe2x88x92, HSO4xe2x88x92, SO42xe2x88x92 an organic acid such as OCOCH3xe2x88x92 and the like. A particularly preferred cationic substituent of B or Bxe2x80x2 is a radical xe2x80x94C(O)OY7 wherein Y7 is C2-C4-alkyl, which is substituted by xe2x80x94N(C1-C2-alkyl)3+Anxe2x88x92 and is further substituted by hydroxy, and Anxe2x88x92 is an anion, for example the radical xe2x80x94C(O)Oxe2x80x94CH2xe2x80x94CH(OH)xe2x80x94CH2xe2x80x94N(CH3)3+Anxe2x88x92.
(iv) Zwitterionic Substituents xe2x80x94R5xe2x80x94Zw:
R5 is a preferably a carbonyl, ester or amide functional group and more preferably an ester groupxe2x80x94C(O)xe2x80x94Oxe2x80x94.
Suitable anionic groups of the moiety Zw are for example xe2x80x94COOxe2x88x92, xe2x80x94SO3xe2x88x92, xe2x80x94OSO3xe2x88x92, xe2x80x94OPO3Hxe2x88x92 or bivalent xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94 or xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94Oxe2x80x94, preferably a group xe2x80x94COOxe2x88x92 or xe2x80x94SO3xe2x88x92 or a bivalent group xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94, and in particular a group xe2x80x94SO3xe2x88x92.
Suitable cationic groups of the moiety Zw are for example a group xe2x80x94NR9R9xe2x80x2R9xe2x80x3+ or a bivalent group xe2x80x94NR9R9xe2x80x2+xe2x80x94, wherein R9, R9xe2x80x2 and R9xe2x80x3 are as defined above, and are each independently of the other, preferably hydrogen or C1-C6-alkyl, preferably hydrogen or C1-C4-alkyl and most preferably each methyl or ethyl.
The moiety Zw is for example C2-C30-alkyl, preferably C2-C12-alkyl, and more preferably C3-C8-alkyl, which is in each case uninterrupted or interrupted by xe2x80x94Oxe2x80x94 and substituted or interrupted by one of the above-mentioned anionic and cationic groups each, and, in addition, is further unsubstituted or substituted by a radical xe2x80x94OY8, wherein Y8 is hydrogen or the acyl radical of a carboxylic acid.
Y8 is preferably hydrogen or the acyl radical of a higher fatty acid.
Zw is preferably C2-C12-alkyl and even more preferably C3-C8-alkyl which is substituted or interrupted by one of the above-mentioned anionic and cationic groups each, and in addition may be further substituted by a radical xe2x80x94OY8.
A preferred group of zwitter-ionic substituents xe2x80x94R5xe2x80x94Z corresponds to the formula
xe2x80x94C(O)Oxe2x80x94(alkxe2x80x2xe2x80x3)xe2x80x94N(R9)2+xe2x80x94(alkxe2x80x2)xe2x80x94Anxe2x88x92 or
xe2x80x94C(O)Oxe2x80x94(alkxe2x80x3)xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94(O)0-1xe2x80x94(alkxe2x80x2xe2x80x3)xe2x80x94N(R9)3+
wherein R9 is hydrogen or C1-C6-alkyl; Anxe2x88x92 is an anionic group xe2x80x94COOxe2x88x92, xe2x80x94SO3xe2x88x92, xe2x80x94OSO3xe2x88x92 or xe2x80x94OPO3Hxe2x88x92, preferably xe2x80x94COOxe2x88x92 or xe2x80x94SO3xe2x88x92 and most preferably xe2x80x94SO3xe2x88x92, alkxe2x80x2 is C1-C12-alkylene, (alkxe2x80x3) is C2-C24-alkylene which is unsubstituted or substituted by a radical xe2x80x94OY8, Y8 is hydrogen or the acyl radical of a carboxylic acid, and (alkxe2x80x2xe2x80x3) is C2-C8-alkylene.
(alkxe2x80x2) is preferably C2-C5-alkylene, more preferably C2-C6-alkylene and most preferably C2-C4-alkylene. (alkxe2x80x3) is preferably C2-C12-alkylene, more preferably C2-C6-alkylene and particularly preferably C2-C3-alkylene which is in each case unsubstituted or substituted by hydroxy or by a radical xe2x80x94OY8. (alkxe2x80x2xe2x80x3) is preferably C2-C4-alkylene and more preferably C2-C3-alkylene. R9 is hydrogen or C1-C4-alkyl, more preferably methyl or ethyl and particularly preferably methyl. A preferred zwitterionic substituent of B or Bxe2x80x2 is of formula
xe2x80x94C(O)Oxe2x80x94CH2xe2x80x94CH(OY8)xe2x80x94CH2xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94(CH2)2xe2x80x94N(CH3)3+,
wherein Y8 is hydrogen or the acyl radical of a higher fatty acid.
In one embodiment of the invention one of B and Bxe2x80x2 may also be the radical of a hydrophobic comonomer which includes especially those customarily used in the manufacture of contact lenses. Suitable hydrophobic vinylic comonomers include, without the list being exhaustive acrylonitrile, methacrylonitrile, vinyl-C1-C18-alkanoates, C2-C18-alkenes, C2-C18-haloalkenes, styrene, C1-C6-alkylstyrene, C2-C10-perfluoroalkyl acrylates and methacrylates or correspondingly partially fluorinated acrylates and methacrylates, C3-C12-perfluoroalkyl-ethyl-thio-carbonylaminoethyl acrylates and methacrylates, acryloxy- and methacryloxy-alkylsiloxanes, N-vinylcarbazole and the like. Examples of suitable hydrophobic vinylic comonomers include acrylonitrile, methacrylonitrile, vinyl acetate, vinyl propionate, vinylbutyrate, vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidene chloride, 1-butene, butadiene, vinyltoluene, perfluorohexylethylthiocarbonylaminoethyl methacrylate, trifluoroethyl methacrylate, hexa-fluoroisopropyl methacrylate, hexafluorobutyl methacrylate, tris-trimethylsilyloxy-silyl-propyl methacrylate, 3-methacryloxypropylpentamethyldisiloxane and bis(methacryloxypropyl)tetramethyidisiloxane.
B denotes for example a radical of formula

wherein R3xe2x80x2 is hydrogen or C1-C4-alkyl, preferably hydrogen or methyl; R6 is a hydrophilic substituent, wherein the above given meanings and preferences apply; R7 is C1-C4-alkyl, phenyl or a radical xe2x80x94C(O)OY9, wherein Y9 is hydrogen or unsubstituted or hydroxy-substituted C1-C4-alkyl; and R8 is a radical xe2x80x94C(O)Y9xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY9xe2x80x2 wherein Y9xe2x80x2 independently has the meaning of Y9.
R7 is preferably C1-C2-alkyl, phenyl or a group xe2x80x94C(O)OY9. R8 is preferably a group xe2x80x94C(O)OY9xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY91 wherein Y9 and Y9xe2x80x2 are each independently of the other hydrogen, C1-C2-alkyl or hydroxy-C1-C2-alkyl. Particularly preferred xe2x80x94CHR7-CHR8xe2x80x94 units according to the invention are those wherein R7 is methyl or a group xe2x80x94C(O)OY9 and R1 is a group xe2x80x94C(O)OY9xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY9xe2x80x2 wherein Y9 and Y9xe2x80x2 are each hydrogen, C1-C2-alkyl or hydroxy-C1-C2-alkyl.
Bxe2x80x2 independently may have one of the meanings given above for B or is the radical of a hydrophobic comonomer, for example the radical of one of the above-given hydrophobic comonomers.
If (oligomer) is a telomer radical of formula (10), the radical xe2x80x94(alk)xe2x80x94Sxe2x80x94[B]pxe2x80x94[Bxe2x80x2]qxe2x80x94Q preferably denotes a radical of formula 
even more preferably of the formula 
wherein for R3xe2x80x2, R6, Q, p and q the above-given meanings and preferences apply, for R3xe2x80x3 independently the meanings and preferences given before for R3xe2x80x2 apply, and for R6xe2x80x2 independently the meanings and preferences given before for R6 apply or R6xe2x80x2 is a hydrophobic substituent selected from the group consisting of hydrogen, xe2x80x94CN, C1-C18-alkanoyl, C1-C16-alkyl, C1-C16-haloalkyl, phenyl, C1-C6-alkylphenyl, C2-C10-perfluoroalkyloxycarbonyl or a corresponding partially fluorinated alkyloxycarbonyl radical, C3-C12-perfluoroalkyl-ethyl-thio-carbonylaminoethyloxycarbonyl, alkylsiloxyloxycarbonyl and carbazolyl.
A preferred group of suitable hydrophilic macromers according comprises compounds of the above formula (9) wherein R4* is hydrogen or methyl, R4 is hydrogen, methyl or carboxyl, R4xe2x80x2 is hydrogen, A3 is a radical of the above formula (6a), (6b) or (6e), wherein n and m are each 0 or 1, X1 X3 and X4 are each independently of the other xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94, Al is unsubstituted or hydroxy-substituted xe2x80x94Oxe2x80x94C2-C8-alkylene or a radical xe2x80x94Oxe2x80x94C2-C6-alkylenexe2x80x94NHxe2x80x94C(O)xe2x80x94, A2 is C1-C4-alkylene, phenylene or benzylene, (alk*) is C2-C4-alkylene, and (oligomer) denotes a radical of formula 
wherein (alk) is C2-C6-alkylene, Q is a monovalent group that is suitable to act as a polymerization chain-reaction terminator, p and q are each an integer of from 0 to 100 and the total of (p+q) is from 5 to 100, R3xe2x80x2 and R3xe2x80x3 are each independently of the other hydrogen or methyl, and for R6 and R6xe2x80x2 each independently of the other the meanings and preferences given before apply.
A more preferred group of suitable hydrophilic macromonomers according to the invention comprises compounds of formula 
wherein R4* is hydrogen or methyl, A1 is xe2x80x94Oxe2x80x94(CH2)2-4xe2x80x94, xe2x80x94Oxe2x80x94CH2xe2x80x94CH(OH)xe2x80x94CH2xe2x80x94 or a radical xe2x80x94Oxe2x80x94(CH2)2-4xe2x80x94NHxe2x80x94C(O)xe2x80x94, X is xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94, (alk) is C2-C4-alkylene, Q is a monovalent group that is suitable to act as a polymerization chain-reaction terminator, p is an integer from 5 to 50, R3xe2x80x2 is hydrogen or methyl, and for R6 the above given meanings and preferences apply.
Particularly preferred macromonomers comprise those of formula 
wherein for R4*, R3xe2x80x2, R6, Q, (alk) and p the above-given meanings and preferences apply. A particularly preferred group of hydrophilic macromonomers are compounds of the above formula (9b) wherein R4* is hydrogen or methyl, (alk) is C2-C4-alkylene, R31 is hydrogen or methyl, p is an integer of 5 to 50, Q is as defined before, and for R6 the above given meanings and preferences apply. Particularly preferably, the radical xe2x80x94CH2xe2x80x94C(R3xe2x80x2)(R6)xe2x80x94 in brackets in formula (9b) is the 1,2-ethylene radical derived from acrylamide, N,N-dimethyl acrylamide or N-vinylpyrrolidone.
The weight average molecular weight of the macromonomers that are optionally employed in the invention depends principally on the desired properties and is for example from 300 to 12000, preferably from 300 to 8000, more preferably from 300 to 5000, and particularly preferably from 500 to 2000.
The macromonomers of formula (9) may be prepared by methods known per se. For example, the compounds of formula (9) wherein A is a radical of formula (6a), (6b) or (6c) are obtainable by reacting a compound of formula 
wherein R4, R4xe2x80x2 and R4* each have the above-given meaning and A* is, for example, a group xe2x80x94C(O)xe2x80x94A**, wherein A** is halogen, particularly chlorine, an ester group an oxyalkylene radical comprising an epoxy group, for example the radical 
or is a radical xe2x80x94Oxe2x80x94
C2-C12-alkylene-Nxe2x95x90Cxe2x95x90O; or A* is a radical xe2x80x94(A2)mxe2x80x94Nxe2x95x90Cxe2x95x90O or xe2x80x94(A4)txe2x80x94Nxe2x95x90Cxe2x95x90O, wherein A2, A4, m and t each have the above-given meaning, with a compound of formula
HXxe2x80x94(oligomer)xe2x80x83xe2x80x83(8a),
wherein X and (oligomer) each have the above-given meaning.
The reactions of a compound of formula (7a) having a carboxylic acid halide group, an epoxy group or an isocyanato group with an amino or hydroxy compound of formula (8a) are well-known in the art and may be carried out, for example, as described above concerning the reaction of the compounds of formula (7) with the compounds of formula (8).
Moreover, the macromonomers of formula (1) wherein A is a radical of formula (6c) or (6e) may be obtained by reacting a compound of formula 
wherein R4, R4xe2x80x2, R4*, A4, X3, X4, (alk*) and t each have the above-given meaning, with a compound of formula
xe2x80x94X1xe2x80x2(O)Cxe2x80x94(oligomer)xe2x80x83xe2x80x83(12),
wherein (oligomer) has the above-given meaning and X1xe2x80x2 is for example xe2x80x94OH or halogen, in particular chlorine, or together with xe2x80x94(O)Cxe2x80x94 forms an anhydride group, in a manner known per se.
The macromonomers of the formula 
wherein (alk*), Xxe2x80x2, X5 and (oligomer) each have the above-given meaning, may be obtained in a manner known per se, for example, by reacting a compound of formula 
wherein (alk*) has the above-given meaning, with a compound of the above-given formula (6), or by reacting a compound of formula 
with a compound of the above formula (8a) wherein (alk*) and X4 each have the above-given meaning.
The compounds of the formula (7a), (8a), (7b), (7c), (7d) and (7e) are known compounds which are commercially available or may be prepared according to known methods. For example, compounds of the formula (7a) and (8a) wherein (oligomer) denotes a radical of formula (6a) and their manufacture are known for example from PCT application WO 92/09639.
The co-grafts-polymerization of one or more acceptor saccharides comprising a Cxe2x80x94C double bond and one or more hydrophilic macromonomers, for example of the above formula (9), may be performed by processes known per se, for example by photopolymerizing a mixture of the acceptor saccharide(s) and the macromonomer(s) according to a process as outlined above.
By means of the above-described coating process, the acceptor saccharides, optionally in admixture with a hydrophilic macromonomer, may be grafted to the bulk material surface with formation of a coating having for example a so-called bottle brush-type structure (BBT) composed of tethered xe2x80x9chairyxe2x80x9d chains. Such BBT structures in one embodiment comprise a long hydrophilic or hydrophobic backbone which carries relatively densely packed comparatively short hydrophilic side chains (called primary bottle brushes). Another embodiment relates to secondary bottle brushes which are characterized in that the hydrophilic side chains themselves carry densely packed hydrophilic xe2x80x9csecondaryxe2x80x9d side chains.
The enzymatical attachment of the further carbohydrate(s) to the acceptor saccharide may take place before or after the covalent bonding of the acceptor saccharide to the surface of the ophthalmic molding. According to one embodiment of the invention, the further carbohydrate(s) are previously enzymatically attached to the acceptor saccharide, for example in solution, and the carbohydrate thus obtained is then, optionally after a work-up or a purification step, covalently bonded to the surface of the ophthalmic molding, for example according to one of the methods as outlined above. According to a further embodiment of the invention, the acceptor saccharide is first of all bonded covalently to the surface of the ophthalmic molding, and to the acceptor saccharides thus immobilized is then enzymatically attached the further carbohydrate(s).
The attachment of a further carbohydrate to an acceptor saccharide immobilized on the substrate surface or in solution occurs advantageously by reacting the carbohydrate with the acceptor saccharide units in the presence of an enzyme, in particular in the presence of a glycosyltransferase. The attachment of the further carbohydrate thus comprises the transfer of a glycosyl group from a donor to an acceptor by means of a specific glycosyl transferase. The donor is suitably an enzyme substrate which is activated with the glycosyl group to be transferred, e.g. a nucleoside. The acceptor saccharides being present on the modified surface of the opthalmic molding or in solution function as acceptor molecules. Glycosyltransferases suitable to aid selectively attaching a carbohydrate, for example the above-mentioned carbohydrates, to an acceptor saccharide are known to the art-skilled worker and can be taken from textbooks of enzyme chemistry, for example from D. Schomburg, D. Stephen (Eds.), Enzyme Handbook 12, Class 2.3.2-2.4, Transferases, Springer Berlin, Heidelberg, New York, Tokyo 1996. The textbook discloses i.a. suitable sialyl transferases, galactosyl transferases, fucosyl transferases, mannosyl transferases, glucosyl transferases or xylosyl transferases.
Suitable reaction media and conditions, for example appropriate enzyme substrates and other optional ingredients such as proteins, buffers and the like are known to the art-skilled worker or conveniently may be taken from the above-mentioned textbooks.
A further embodiment of the invention comprises further sulfating the primarily generated surfacexe2x80x94comprising the covalently bonded acceptor saccharides and the enzymatically attached further carbohydratexe2x80x94enzymatically by using, for example, adenosine-3xe2x80x2-phosphate-5xe2x80x2-phosphosulfate (PAPS) as donor moiety and a sulfo-transferase as enzyme.
The enzymatic attachment of carbohydrates according to the invention enables one to generate complex oligo- or polysaccharide structures on the surface of the ophthalmic molding by applying one or more different carbohydrates, in particular one or more different monosaccharides, in the presence of one or more different glycosyltransferases. In case of different carbohydrates to be attached, the enzymes may be applied sequentially one-by-one or as combinations of several enzymes, together with the corresponding enzyme substrate in each case. Depending on the nature of the terminal sugar radicals present on the modified surface obtained, the enzymes elongate and/or crosslink the carbohydrate structure on the material surface in accordance with the specifity of the enzymes and the substrates present in the reaction mixture.
The coating thickness of the carbohydrate coating comprising the acceptor saccharides and the enzymatically attached further carbohydrates on the surface of the ophthalmic molding depends principally on the desired properties. It can be, for example, from 0.001 to 1000 xcexcm, preferably from 0.01 to 500 xcexcm, more preferably from 0.01 to 100 xcexcm, even more preferably from 0.05 to 50 xcexcm, especially preferably from 0.1 to 5 xcexcm and particularly preferably from 0.1 to 1 xcexcm.
The carbohydrate modified surfaces of the ophthalmic moldings obtained according to the invention may be purified afterwards applying conventional techniques such as for example washing or extraction with a solvent like water, methanol, ethanol and the like. The characterization of the surfaces obtained may be performed by various techniques including X-ray Photoelectron Spectroscopy (XPS) or Time Of Flight Secondary Ion Mass Spectrometry (TOF-SIMS).
Suitable ophthalmic moldings according to the invention are, for example, contact lenses including both hard and particularly soft contact lenses or any kind of ocular prostheses such as corneal implants, in particular intraocular lenses or artificial cornea.
The ophthalmic devices according to the invention have a variety of unexpected advantages over those of the prior art which make those devices very suitable for practical purposes, e.g. as contact lens for extended wear or intraocular lens. For example, they do have a high surface wettability which can be demonstrated by their contact angles, their water retention and their water-film break up time or tear film break up time (TBUT).
The TBUT plays an particularly important role in the field of ophthalmic devices such as contact lenses. Thus the facile movement of an eyelid over a contact lens has proven important for the comfort of the wearer; this sliding motion is facilitated by the presence of a continuous layer of tear fluid on the contact lens, a layer which lubricates the tissue/lens interface. However, clinical tests have shown that currently available contact lenses partially dry out between blinks, thus increasing friction between eyelid and the lens. The increased friction results in soreness of the eyes and reduced movement of the contact lenses. Taking into account the average time period between two blinks of an eye it follows that a wettable and biocompatible contact lens should hold a continuous layer of tear fluid for more than 10 seconds and preferably for more than 15 seconds. Whereas current biomedical materials in general have TBUTs of well below 10 seconds and thus do not reach this target, the composite materials of the present invention have TBUTs of  greater than 10 seconds and especially  greater than 15 seconds. In addition, the TBUT of commercial contact lenses may be improved considerably by applying a surface coating according to the invention. On the base curve of a contact lens, the pronounced lubricity of the coating facilitates the on-eye lens movement which is essential for extended wear of contact lenses. Moreover, the moldings of the invention provide additional effects being essential for lenses for extended wear, such as an increased thickness of the pre-lens tear film which contributes substantially to low microbial adhesion and resistance to deposit formation. Due to the extremely soft and lubricious character of the novel surface coatings, the ophthalmic moldings of the invention such as in particular contact lenses show a superior wearing comfort including improvements with respect to late day dryness and long term (overnight) wear. The novel surface coatings moreover interact in a reversible manner with occular mucus which contributes to the improved wearing comfort.
In addition, ophthalmic devices obtainable according to the present invention have a very pronounced biocompatibility combined with good mechanical properties. For example, the devices are blood compatible and have a good tissue integration. In addition, there are generally no adverse eye effects observed, while the adsorption of proteins or lipids is low, also the salt deposit formation is lower than with conventional contact lenses. Generally, there is low fouling, low microbial adhesion and low bioerosion while good mechanical properties can be for example found in a low friction coefficient and low abrasion properties. Moreover, the dimensional stability of the ophthalmic moldings of the invention is excellent. In addition, the carbohydrate modified surface on a given bulk material according to the invention does not affect its visual transparency.
In addition, the moldings of the present invention having a carbohydrate modified surface are capable of interacting with human or animal tissue cells and support the attachment and growth of human or animal cells in vivo or in vitro, which make those devices very suitable for practical purposes, e.g. as corneal implant, in particular as intraocular lens or artificial cornea.
Corneal implants may be placed by way of conventional surgery techniques beneath, within, or through corneal epithelial tissue, or within the corneal stroma or other tissue layers of the cornea. Such implants may change the optical properties of the cornea (such as to correct visual deficiencies) and/or change the appearance of the eye, such as pupil coloration. A corneal implant may comprise an optical axis region which on implantation covers the pupil and provides visual acuity, and a less transparent region which surrounds the periphery of the optical axis region. Alternatively the implant may have the same visual acuity across its dimensions.
In summary, the ophthalmic devices according to the invention, such as contact lenses and artificial cornea, provide a combination of (i) low spoilation with respect to cell debris, cosmetics, dust or dirt, solvent vapors or chemicals, (ii) a high comfort for the patient wearing such opthalmic devices in view of the soft hydrogel surface which for example provides a very good on-eye movement of the ohthalmic device and (iii) biocompatibility, bioadhesion, cell accumulation, molecular recognition and cell attachment.
In the examples, if not indicated otherwise, amounts are amounts by weight, temperatures are given in degrees Celsius. Tear break-up time values in general relate to the pre-lens tear film non-invasive break-up time (PLTF-NIBUT) that is determined following the procedure published by M. Guillon et al., Ophthal. Physiol. Opt. 9, 355-359 (1989) or M. Guillon et al., Optometry and Vision Science 74, 273-279 (1997). Average advancing and receding water contact angles of coated and non-coated lenses are determined with the dynamic Wvilhelmy method using a Krxc3xcss K-12 instrument (Krxc3xcss GmbH, Hamburg, Germany). Wetting force on the solid is measured as the solid is immersed in or withdrawn from a liquid of known surface tension.